This is a six center, double blind, placebo controlled study to determine if the administration of oral doxycycline will decrease the severity or progression of osteo-arthritis in females. This is a 30-month clinical trial. Because the pathologic changes of OA progress slowly, obese women, between ages of 45-64 with radiographic evidence of unilateral knee OA will be used as subjects. Our primary outcome measure will be radiographic OA progression in the contralateral knee.